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Writer's pictureJason Cafer MD

Ketogenic diet for Serious Mental Illness

ketogenic diet for serious mental illness

What is the Ketogenic Diet?


The ketogenic diet (KD) is a high-fat, adequate-protein, low-carbohydrate diet. When glucose intake is reduced, the body shifts to using fat as its primary energy source, a process known as ketogenesis. During ketogenesis, the liver breaks down fatty acid

to produce ketone bodies, primarily acetoacetate, acetone, and β-hydroxybutyrate. These ketone bodies become the primary energy source for the central nervous system.


Potential of the KD in Treating Psychiatric Disorders

While the KD is an established non-pharmacological treatment for epilepsy, emerging research suggests that it may also hold therapeutic potential for individuals with serious mental illnesses (SMI) such as:


  • Bipolar Disorder

  • Major Depressive Disorder

  • Schizophrenia


Several underlying mechanisms in the pathophysiology of mental illness may be influenced by the KD. For example, the KD has been shown to:

  • Alleviate inflammation and oxidative stress: Both of these are implicated in various psychiatric disorders

  • Modulate the gut microbiota community: Imbalances in gut bacteria have been linked to mental health conditions.

  • Improve metabolic health markers: Individuals with SMI often experience metabolic abnormalities.


Research Findings


Preliminary research suggests a potential therapeutic effect of the KD on SMI, including:

  • Weight reduction

  • Improvements in carbohydrate and lipid metabolism

  • Reduction in disease-related symptoms

  • Increased energy and quality of life

  • Potential changes in pharmacotherapy (reduction in medication number or dosage)


However, it's essential to note that much of the existing research on the KD's effects on SMI is based on:

  • Case studies: These offer limited generalizability.

  • Small-scale clinical trials: Larger studies are needed to confirm preliminary findings.


Some notable findings from studies on the KD's impact on specific mental illnesses include:


Schizophrenia:

  • A pilot study showed that patients with schizophrenia on a KD for four months experienced:

    • Significant weight loss (12%)

    • Improvements in metabolic health

    • A 32% reduction in Brief Psychiatric Rating Scale scores

    • Improved overall clinical global impression severity (31%)

  • Animal studies also indicate that the KD can:

    • Regulate abnormal behaviors in a mouse model of schizophrenia

    • Prevent sensory gating deficiencies

    • Protect against antipsychotic-induced hyperglycemia


Depression:

  • A case study found that a 65-year-old woman with major depressive disorder experienced:

    • Remission of depressive symptoms after following a KD for three months

    • Reduction in medication usage

    • Improvements in weight, blood pressure, blood glucose, and triglycerides

  • Animal research indicates that the KD may:

    • Have antidepressant-like effects

    • Reduce susceptibility to depressive and anxiety states


Bipolar Disorder:

  • A pilot study involving 16 individuals with bipolar disorder on a KD for four months showed:

    • Increased life satisfaction

    • Enhanced sleep quality

    • Improvements in the severity of mental illness for 69% of participants

  • Case studies and online forum analyses also suggest potential benefits of the KD for bipolar disorder, such as:

    • Mood stabilization

    • Reduction in depressive episodes

    • Improved cognitive function and concentration


Important Considerations for Psychiatrists


Initiating the KD for patients with SMI should always be done with caution and under the supervision of a physician and a registered dietitian. This is due to:

  • Potential side effects of the diet: These may include headache, fatigue, constipation, and electrolyte imbalances, though often subside after the initial weeks.

  • Potential for exacerbating adverse effects of pharmacotherapy: The KD can interact with certain medications


Key interactions between ketogenic diet and medications

Lithium:
  • Initial diuretic effect from ketosis causes fluid shifts

  • Hyponatremia elevates lithium

    • Because lithium competes with sodium for renal resorption

  • Lithium levels can increase 20-35% in the first 2-4 weeks of keto

  • Management:

    • More frequent lithium level monitoring first month

    • Maintaining adequate hydration/electrolytes (LMNT or Re-Lyte)

    • May need lithium dose reduction

    • Gradual rather than abrupt diet transition

Interaction lithium with ketogenic diet
Valproic Acid:
  • VPA competes with ketones for protein binding

  • May increase free drug levels without affecting total VPA as routinely reported

    • Consider checking free VPA level


Warfarin:
  • Altered absorption due to high fat intake

  • Changes in vitamin K intake affect INR

  • Requires closer monitoring


Diuretics:
  • Increased risk of dehydration/electrolyte imbalance

  • Enhanced natriuretic effect


Psychiatrists should consider the following when deciding on the suitability of the KD for a patient:

  • Patient's individual characteristics: Factors such as age, overall health status, lifestyle, and medication regimen should be taken into account.

  • Potential risks and benefits: A thorough discussion of these should be conducted with the patient.

  • Need for ongoing monitoring: Regular check-ups are crucial to assess the diet's impact on both mental and physical health.


Ongoing Research

A significant number of clinical trials are currently underway to further investigate the KD's impact on psychiatric disorders. These studies are crucial for:

  • Confirming the preliminary findings from smaller studies.

  • Establishing the long-term efficacy and safety of the KD for SMI.

  • Identifying the optimal protocols for implementing the KD in clinical practice.


Conclusion

The KD presents a promising avenue for adjunctive treatment in individuals with SMI. Early research suggests potential benefits for various mental health conditions, particularly in improving metabolic health and reducing symptom severity. However, larger-scale, long-term studies are needed to confirm these findings and guide clinical practice. Psychiatrists should exercise caution and collaborate with dietitians to ensure the safe and effective implementation of the KD for their patients.


  1. Sethi, S., Wakeham, D., Ketter, T., Hooshmand, F., Bjornstad, J., Richards, B., ... & Saslow, L. (2024). Ketogenic Diet Intervention on Metabolic and Psychiatric Health in Bipolar and Schizophrenia: A Pilot Trial. Psychiatry research, 335, 115866.

  2. Rog, J., Wingralek, Z., Nowak, K., Grudzień, M., Grunwald, A., Banaszek, A., & Karakula-Juchnowicz, H. (2024). The Potential Role of the Ketogenic Diet in Serious Mental Illness: Current Evidence, Safety, and Practical Advice. Journal of Clinical Medicine, 13(10), 2819.

  3. Mentzelou, M., Dakanalis, A., Vasios, G. K., Gialeli, M., Papadopoulou, S. K., & Giaginis, C. (2023). The relationship of ketogenic diet with neurodegenerative and psychiatric diseases: a scoping review from basic research to clinical practice. Nutrients, 15(10), 2270.

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